摘要：SummaryCurrent adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from T cells and succeeded in regenerating CTLs specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. In this study, we extended our strategy to solid tumors. The regenerated WT1-specific CTLs had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma (RCC) cell line. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specificTCR α/βgenes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of RCC, demonstrating the feasibility of our strategy against solid tumors.Graphical AbstractDisplay OmittedHighlights•Patient-derived xenograft of renal cell carcinoma was used in a cell-therapy model•Cytotoxic T lymphocytes (CTLs) that target WT1-antigen were used as effector cells•CTLs produced from iPSCs transduced with WT1-TCR genes showed efficacy in the model•The present results demonstrate the feasibility of our strategy against solid tumorsCellular Therapy; Immunological Methods; Cancer
